Cancer Treatment

• The three major forms of treatment for any cancer are

1. Surgery (removing the cancer), 
2. Radiotherapy (delivering ionising radiation to the tumour), 
3. Systemic therapy (administering medicines that act on the tumour). 

• Surgery and radiotherapy have been refined significantly over time, whereas advances in systemic therapy have been unparalleled. 
• A new development on this front, currently holding the attention of many researchers worldwide, is CAR T-cell therapy.

Earlier forms of systemic therapy

• Chemotherapy 

• Chemotherapy,when administered, preferentially acts on cancer cells because of the latter’s rapid, unregulated growth and poor healing mechanisms. 
• Chemotherapeutic drugs have modest response rates and significant side-effects as they affect numerous cell types in the body.

• Immunotherapy

• The drugs bind to specific targets on the cancer or in the immune cells that help the tumour grow or spread.
• This method often has fewer side-effects as the impact on non-tumour cells is limited. 
• However, it is effective only against tumours that express these targets.

CAR T-cell Therapy

• CAR T-cell therapies use a patient’s own cells. 
• They are modified in the laboratory to activate T-cells, a component of immune cells, to attack tumours.
• These modified cells are then infused back into the patient’s bloodstream after conditioning them to multiply more effectively.
• The cells are even more specific than targeted agents and directly activate the patient’s immune system against cancer, making the treatment more clinically effective. This is why they’re called ‘living drugs’.

How it works

• In CAR T-cell therapy, the patient’s blood is drawn to harvest T-cells – immune cells that play a major role in destroying tumour cells
• Researchers modify these cells in the laboratory so that they express specific proteins on their surface, known as chimeric antigen receptors (CAR): they have an affinity for proteins on the surface of tumour cells. 
• This modification in the cellular structure allows CAR T-cells to effectively bind to the tumour and destroy it.
• In CAR T-cell therapy, the immune system is activated when the modified T-cells are reintroduced into the body, which allows a gradual and sustained tumour kill as these cells multiply

Where it is used

• CAR T-cell therapy has been approved for leukaemias (cancers arising from the cells that produce white blood cells) and lymphomas (arising from the lymphatic system)
• For solid tumours – like those of the prostate, lung, colon, and some other organs – CAR T-cell therapy has been shown to be able to cure patients with tumours that have recurred or have evaded multiple lines of treatment.
• However, These are highly heterogeneous cancers that lack a consistent target with which CAR T-cells can bind.
• CAR T-cell therapy is also presently used among patients with cancers that have returned after an initial successful treatment or which haven’t responded to previous combinations of chemotherapy or immunotherapy.

Response rate of CAR-T cell therapy

• Its response rate is variable.
• In certain kinds of leukaemias and lymphomas, the efficacy is as high as 90%, whereas in other types of cancers it is significantly lower. 

Side Effects

• The potential side-effects are also significant, associated with cytokine release syndrome (a widespread activation of the immune system and collateral damage to the body’s normal cells) and neurological symptoms (severe confusion, seizures, and speech impairment).

Barriers to the use of CAR-T therapy

• • The complexity of preparing CAR T-cells has been a major barrier to their use. 
  • The first clinical trial showing they were effective was published almost a decade ago; the first indigenously developed therapy in India was successfully performed only in 2021.
  • The technical and human resources required to administer this therapy are also considerable. 

• Treatments in the US cost more than a million dollars.

• Critics argue that developing facilities in India may be redundant and/or inappropriate as even when it becomes cheaper, CAR T-cell therapy will be unaffordable to most Indians.

Potential of the therapy

• Progress in the field, however, has the potential to unlock a host of newer treatments on the horizon called cell therapies.
• They include personalised anti-cancer vaccines and tumour infiltrating lymphocyte therapies (where white blood cells that attack the tumour are extracted, modified, and reintroduced into the patient).

https://www.thehindu.com/sci-tech/science/explained-why-car-t-cell-therapy-is-cancer-treatments-next-moonshot/article66478184.ece